This invention relates to a dietary supplement for use in a weight loss program, which alleviates insulin resistance in the presence of the metabolic syndrome.
The metabolic syndrome, an increasingly common disorder associated with obesity, is a cluster of metabolic derangements that are associated with a significant increase in risk of cardiovascular disease. The syndrome is linked with primary disturbances in adipose tissue due to an excessive accumulation of visceral (intra-abdominal) fat in genetically susceptible individuals. The increased adipocyte mass assumes the role of an endocrine organ, communicating with other organ systems via a release of hormonal-like chemicals called inflammatory cytokines. The resulting disorders include insulin resistance and hyperlipidaemia (elevated blood cholesterol), hypertension and diabetes.
It is generally accepted that, for a diabetic, improved glycaemic control can lower cardiovascular risk. It has, however, also been demonstrated that in most cases diabetic medication, in particular the use of insulin, actually causes weight gain, often in individuals that are already overweight or obese. Clearly, iatrogenic (caused by medication) weight gain is not only unwelcome, but is also counterproductive. Limiting insulin-associated weight gain has therefore become a new treatment challenge.
Different strategies have been proposed to prevent or treat the development of obesity and the consequences of the metabolic syndrome. These include increased physical activity such as cardiovascular exercise for at least 30 minutes every day, and a healthy, calorie-reduced diet. There are studies that support the value of a healthy lifestyle, but it can be argued that these measures are effective in only a minority of people, primarily due to a lack of compliance with lifestyle and dietary changes.
Drug treatment is frequently required. Generally, the individual disorders such as hypertension, dyslipidaemia and diabetes that comprise the metabolic syndrome, are treated separately. In the absence of diabetes, however, the use of diabetic drugs for the treatment of insulin resistance in an overweight person is still controversial and, to the applicant's knowledge, no product has to date been approved by the Food and Drug Administration. Whilst insulin, the sulphonylureas and the thiazolidinediones are known to cause weight gain, metformin does not interfere with body mass and has therefore become a drug of choice.
Various studies have investigated the role that insulin plays in weight gain. In the United Kingdom Prospective Diabetes Study (UKPDS), for example, increased weight gain was directly related to improved glycaemic control and intensification of therapy with all pharmacotherapies, with the exception of metformin. However, weight gain was greatest in a group treated with insulin, where patients gained on average 6.5 kg. In addition, data from the Diabetes Control and Complication Trial (DCCT) demonstrated that insulin-associated weight gain was significantly greater in patients receiving intensified insulin intervention, as compared to conventional intervention.
Given that improved glycaemic control also improved the outcome of microvascular disease in the UKPDS and DCCT, it can be argued that the ‘price’ for improved glycaemic control against weight gain is a fair exchange. However, this historic argument makes a rather simplistic assumption when there is evidence that weight gain adversely affects cardiovascular risk. Excess adipose tissue is associated with increased levels of insulin resistance, which not only contributes to dyslipidaemia, but can also fuel a cycle of beta cell dysfunction, increased insulin resistance, a greater requirement for insulin and, ultimately, further weight gain. Besides potentially undermining the cardiovascular benefits of improved glycaemic control, weight gain is known to accelerate some disease processes that underlie diabetes. In this context, weight gain should be viewed as an undesirable side-effect of insulin and other obesity-promoting oral diabetic agents, making the use of insulin-sparing strategies an attractive option.
Insulin is an important controller of organic metabolism. It acts both directly and indirectly on most bodily tissues. Its actions can be divided into two broad categories:                a) its metabolic effects on carbohydrate, lipid, and protein synthesis; and        b) its growth-promoting effects on DNA synthesis, mitosis and cell differentiation.In general, metabolic effects occur almost immediately after a physiological rise in insulin concentration, whereas the growth-promoting effects require more time (hours and days) after exposure to elevated insulin concentrations to manifest themselves.        
Insulin has several different effects that lead to fat accumulation in adipose tissue. Firstly, insulin promotes fat synthesis. When the quantity of glucose that enters the liver cells is more than what can be stored as glycogen, insulin promotes the conversion of excess glucose into fatty acids. These fatty acids are subsequently packaged as triglycerides in very low density lipoproteins and transported to the adipose tissue where they are deposited as fat. However, insulin also increases the utilisation of glucose by most of the body's tissues, which automatically decreases the utilisation of fat, thus functioning as a “fat sparer”.
Secondly, insulin plays a role in fat storage. By inhibiting the action of hormone-sensitive lipase, an enzyme that causes hydrolysis of the triglycerides already stored in the fat cells, insulin inhibits the release of fatty acids into the circulating blood stream, thereby promoting obesity. Insulin also promotes glucose transport through the cell membrane into the fat cells in the same way that it promotes glucose transport into the muscle cells. Although some of this glucose is then utilized to synthesize small amounts of fatty acids, the glucose also forms large quantities of glycerophosphate which supplies the glycerol backbone that combines with fatty acids to form triglycerides molecules which are a dominant storage form of fat in adipose cells. Therefore, when insulin is not available, storage of a large amount of fatty acids transported from the liver via lipoproteins is almost totally blocked.
An object of the present invention is to provide a dietary supplement which, in a preferred embodiment, is intended to address at least some of the aforementioned factors.